DESCRIPTION: State the application's broad^B-term objectives and specific aims, making referend^Bthe health relatedness of the project. Describe concisely the research design and methods fwPfhieving these goals. Avoid summaries of past accCT^FIshments and the use of the first person. This description is meant to serve as a succinct and accurate description of the proposed work when separatedfrom the application. If the application is funded, this description, as is, will become public information. Therefore, do not include proprietary/confidential information. DO NOT EXCEED THE SPACE PROVIDED. The GI training program of the Massachusetts General Hospital (MGH) is dedicated to the preparation of investigators committed to a career in GI biomedical research. This program continues to build on its outstanding past experience in establishing productive and committed investigators. Fundamental features of the post-doctoral training format, the major component of this program, include -direct research participation in conjunction with a comprehensive program of didactic instruction and enrichment activities to provide a deep foundation in biomedical science and modern research techniques. In addition, a two-year pre-doctoral laboratory research program is proposed to attract minority students to careers in GI research. (A) Research Areas and Disciplines. Although the strength of the research base of this program encompasses a spectrum of research interests, an intensive experience in the related basic disciplines is a common element of each trainee's experience. The majority of trainees will undertake training in laboratory research in which emphasis is placed on the application of tools of molecular biology to GI research. Training is offered in several disciplines: Molecular Biology, Biochemistry, Membrane Biology, Developmental Biology, Genetics, and Immunology. These disciplines are applied to nine research themes central to the current study of digestive diseases. For the few trainees undertaking training in clinical investigation, a rigorous preparation in relevant quantitative sciences, includingBiostatistics and Epidemiology, is provided. (B) Level of Training. Background and Numbers of Trainees. This renewal proposes both post-doctoral and pre-doctoral training. Post-doctoral training is offered to individuals holding M.D.,M.D.-Ph.D. or relevant Ph.D. degrees. Six post-doctoral positions are requested: three post-doctoral fellows will begin training each year, and remain in research training for a minimum of two years supported by this award. In addition, two positions are requested to continue the recently initiated pre-doctoral training fellowship for minority students completing an undergraduate degree or enrolled in medical school. (C) Training Facilities. Research training will take place in the existing laboratories of the research mentors; a group of established investigators with extensive existing interactions. Laboratories are present in the main campus of the MGH,a large general hospital with more than 250,000 sq. ft. of space dedicated to research, as well as its new campus designated MGH-East, comprised of more than 400,000 sq. ft. of additional research space. In addition, training opportunities will be available in laboratories of the Whitehead Institute (M.l.T. and Harvard University). Didactic educational programs will include those offered through the Harvard Medical School, the Harvard School of Public Health, Harvard University and M.l.T. PERFORMANCE SITE(S)(organization, city, state) Massachusetts General Hospital, Boston, MA (MGH) KEY PERSONNEL. See instructions on Page 11. Use continuation pages as needed to provide the required information in the format shown below. Name Organization Role on Project Podolsky, MD, Daniel K. Massachusetts General Hospital (MGH)/ Director Harvard Medical School (HMS) Alt, Ph.D., Frederick W. Children's Hospital Preceptor Arnaout, M.D., Amin M MGH/HMS Preceptor Ausiello, M.D., Dennis A. MGH/HMS Preceptor Avruch, M.D., Joseph MGH/HMS Preceptor Bhan, M.D,Atul K. MGH/HMS Preceptor Brown, Ph.D., Dennis MGH/HMS Preceptor Calderwood, M.D., Stephen B. MGH/HMS Preceptor Chung, M.D., Daniel C. MGH/HMS Preceptor Chung, M.D., Raymond T. MGH/HMS Preceptor Dienstag, M.D., Jules L. MGH/HMS Preceptor - Fishman, M.D., Mark C. MGH/HMS Preceptor Goldberg, M.D., Marcia MGH/HMS Preceptor Habener, M.D., Joel MGH/HMS Preceptor PHS 398 (Rev. 4/98) Page 2 BB Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b. [unreadable] BB Principal Investigator/Program Director (Last, first, middle): Podolsky. Daniel K. Haber, M.D., Ph.D., Daniel A. H/HMS Preceptor Harlow, Jr.,Ph.D., Edward E. H/HMS Preceptor Kaplan, M.D., Ph.D., Lee M. MGH/HMS Preceptor Kirschner, Ph.D., Marc W. HMS Preceptor Koh, M.D, Theodore J. MGH/HMS Preceptor Luster, M.D, AndrewD. MGH/HMS Preceptor Mashimo, M.D,Ph.D., Hiroshi MGH/HMS Preceptor Melton, Ph.D., Douglas A. Harvard University Preceptor Mulley, M.D, Albert G. MGH/HMS Preceptor Nagler-Anderson, Cathryn MGH/HMS Preceptor Nishioka, M.D, Norman S. MGH/HMS Preceptor Filial, M.D, Ph.D., Shiv S. MGH/HMS Preceptor Reinecker, M.D,Hans-Christian MGH/HMS Preceptor Sachs, M.D, David H. MGH/HMS Preceptor Sands, M.D, Bruce E. MGH/HMS Preceptor Schmidt, M.D, Ph.D., Emmett V. MGH/HMS Preceptor Seed, Ph.D., Brian MGH/HMS Preceptor Singer, M.D, Daniel E. MGH/HMS Preceptor Snapper, M.D, Ph.D., Scott B. MGH/HMS Preceptor Takahashi, M.D,Ph.D,Hiroshi MGH/HMS Preceptor Walker, M.D, W. Allan MGH/HMS Preceptor Wang, M.D, Timothy C. MGH/HMS Preceptor Xavier, M.D, Ramnik J. MGH/HMS Preceptor PHS 398 (Rev. 4/98) Page 3 BB Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b. X NN Principal Investigator/Program Director (Last, first, middle): Podolsky. Daniel K. Type the name of the program director at thd^Hof each printed page and each continuation page.^Hr type specifications, see instructions on page 6.) INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARD (Substitute Page)